Poster Session J - Pathological and Oncological Sciences 1.
Dr. Paál, Ágnes
E8NM06
MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University
06205204926
paal.agnes@semmelweis.hu
Effects of Blunting Annexin A1 Expression in Small Cell Lung Cancer Cell Lines
Paál Ágnes1,2, Takács Ákos3, Varga V. Zoltán1,2,3, Peták István3, Kovács Tamás1,2,3, Ferdinandy Péter3, Görbe Anikó3, Dóra Dávid4
1: HCEMM-SU Cardiometabolic Immunology Research Group, Department of Pharmacology and Pharmacotherapy, Budapest, Hungary
2: MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary
3: MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University
4: Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University
Poszter
Poster Session J - Pathological and Oncological Sciences 1.
Hungarian
Pathological and Oncological Sciences
Introduction
Small cell lung cancer (SCLC) is one of the malignancies with the worst prognosis, for which there have been no major breakthroughs in treatment for a long time. Therefore, characterization of molecular mechanisms behind therapy resistance has relevance in finding novel therapeutic approaches. There are studies showing direct effects of annexin A1 (ANXA1) modulation on cancer cell proliferation. We aimed to investigate the effects of silencing ANXA1 expression in an SCLC cell line.
Aims
We hypothesized that silencing ANXA1 expression in cell culture influences malignant phenotype in vitro, such as growth rate and epithelio-mesenchymal transition, which could highlight roles of ANXA1 in SCLC therapy outcome.
Methods
An SCLC cell line with high ANXA1 expression (H1048) was transfected with control or ANXA1 silencing Lentiviral short hairpin RNA vector. As a selection agent, 0,1% puromycin was present in culture medium. Success of ANXA1 silencing was tested with western blot. Growth rate of control transfected and ANXA1 silenced cells was compared with 120-hour-long trypan blue exclusion assay. Expression of mesenchymal markers, vimentin and ß-catenin was evaluated with western blot. Statistical analysis was done with two-way ANOVA for the trypan blue assay, and one-way ANOVA for the western blots. The n number of the groups was 7-8 (n=7-8) in each experiment.
Result
Annexin A1 expression was stably silenced with Lentiviral shRNA vector, shown by western blots. Growth rate of ANXA1 silenced cells was unexpectedly higher than the native and control shRNA transfected SCLC cells. ANXA1-silenced cells showed less mesenchymal morphology in culture, which observation was supported by decreased mesenchymal marker expression on western blots.
Conclusion
Modulation of ANXA1 expression resulted in mixed effects on the SCLC cell line used. An inhibitory effect on growth rate was not detected in H1048 cell line, which suggests that annexin A1 is probably not an optimal therapeutic target. However, decreased mesenchymal phenotype of ANXA1-silenced cells is a feature that supports complex mechanisms in aggressiveness of this cancer, demanding further research.
Funding
RRF-2.3.1-21-2022-00003, Horizon 2020 No. 739593, Momentum Research Grant Hungarian Academy of Sciences LP-2021-38 to ZVV, NKFIH of Hungary K139237 to AG, SE250+ Excellence Fellowship to ÁP
Semmelweis University
Görbe Anikó
I do not give consent to the publication of my abstract on the website of the congress.
Szabad
elfogadva
poszter
nem rendelkezett róla
7414
16:50
16:53